MUC1-like tandem repeat proteins are broadly immunogenic in cancer patients.
MUC1-like tandem repeat proteins are broadly immunogenic in cancer patients.
复制标题
DOI：
--
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
J. Mollick;F. Hodi;R. Soiffer;L. Nadler;G. Dranoff
中科院分区：
文献类型：
--
作者：
J. Mollick;F. Hodi;R. Soiffer;L. Nadler;G. Dranoff
介导肿瘤排斥反应的抗原的鉴定是癌症免疫学的重要目标。SEREX技术利用来自癌症患者的抗体从肿瘤来源的cDNA表达文库中鉴定候选抗原。使用来自长期存活的转移性黑色素瘤患者的血清，该患者接种了经辐照的自体肿瘤细胞以分泌粒细胞-巨噬细胞集落刺激因子（GM-CSF），我们鉴定了一种抗原，该抗原被报道为推定的阿片样生长因子受体（OGFr）。对OGFr的人类免疫应答表现出与其他肿瘤抗原共有的三个特征。首先，该蛋白是细胞核和细胞质中发现的细胞内抗原。第二，部分抗体反应针对由替代阅读框（ARF）编码的推定蛋白质产物。第三，部分抗体反应针对与MUC 1的胞外结构域在一级结构和大小多态性方面具有惊人相似性的分子部分。在癌症患者中经常发现对OGFr和代表推定的替代阅读框架产物（OGFr-ARF）的合成肽的抗体应答。11/45例（24%）黑色素瘤患者有OGFr抗体，5/45例（11%）有OGFr-ARF抗体。此外，5/24（21%）肺癌，4/25（16%）前列腺癌，和5/6乳腺癌或卵巢癌患者有抗体OGFr，替代框架产品，或两者兼而有之。这些数据增加了似乎在两个框架中翻译的肿瘤抗原的不断增长的列表，并表明OGFr和OGFr-ARF可能是疫苗接种的有用靶点。
The identification of antigens mediating tumor rejection is an important goal of cancer immunology. The SEREX technology utilizes antibodies from cancer patients to identify candidate antigens from tumor-derived cDNA expression libraries. Using sera from a long-term surviving metastatic melanoma patient vaccinated with irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), we identified an antigen reported to be a putative opioid growth factor receptor (OGFr). The human immune response to OGFr exhibits three features shared with other tumor antigens. First, the protein is an intracellular antigen found in both nucleus and cytoplasm. Second, part of the antibody response is directed at a putative protein product encoded by an alternative reading frame (ARF). Third, part of the antibody response is directed at a portion of the molecule that bears a striking resemblance to the extracellular domain of MUC1, both with respect to primary structure and size polymorphism. Antibody responses to OGFr and a synthetic peptide representing a putative alternative reading frame product (OGFr-ARF) were frequently found in cancer patients. 11/45 (24%) melanoma patients had antibodies to OGFr and 5/45 (11%) had antibodies to OGFr-ARF. Moreover, 5/24 (21%) lung cancer, 4/25 (16%) prostate cancer, and 5/6 breast or ovarian cancer patients had antibodies to OGFr, the alternative frame product, or both. These data add to the growing list of tumor antigens that appear to be translated in two frames, and suggest that OGFr and OGFr-ARF may be useful targets for vaccination.